JNeurosci: Highlights from the March 22 issue

Diseases of the retina (the thin sheet of cells at the back of the eye), such as age-related macular degeneration, involve the breakdown of light-sensitive neurons called photoreceptors. The mechanisms responsible for the deterioration of these cells are unclear and many patients go untreated as their vision declines. In a new study, researchers found an established drug approved to treat breast cancer, tamoxifen, protected against photoreceptor degeneration in two different mouse models: a light-induced injury model and another model involving a genetic mutation that causes retinal disease in both mice and humans. This finding was unexpected because tamoxifen has been previously linked to retinal toxicity. The researchers found that tamoxifen works by reducing activation of microglia — the central nervous system's immune cells — and diminishing the production of inflammatory molecules. Based on these results, the researchers suggest tamoxifen may be a candidate for clinical study as a potential treatment for retinal diseases.

The powerful pain reliever morphine is known to be less effective for women compared to men, and a new study in rats reveals a possible explanation. Researchers showed that, compared to male rats, female rats display an increased activation of microglia in the periaqueductal gray, a brain region where opioids like morphine act to alter our experience of pain. They also find that, in females, blocking one of the receptors to which morphine binds, TLR4, renders females similarly responsive to morphine as males. The research suggests that, if this finding translates to humans, TLR4 could be targeted to reduce the dose needed for women to achieve similar levels of pain relief from morphine as men. Lower doses would reduce the risk of the pain medication's negative side effects, such as dependency.

Forming new memories becomes increasingly difficult as we get older, which may be due in part to the degeneration, or atrophy, of brain structures crucial for memory formation. Accumulation of the beta amyloid (Aß) and tau proteins, which has been implicated in the progression of Alzheimer's disease, is also common in healthy older adults. However, the relationships between these changes in the aging brain and their influence on memory ability are not well understood. Researchers recruited healthy older (aged 64-93 years) and younger (aged 18-30 years) adults to participate in a new neuroimaging study designed to test age-related changes in the brain's memory network. While their brain activity was recorded, participants were shown a series of objects and asked to report whether the object was novel, a repeat, or similar to one they had seen before. The researchers found that Aß and tau impacted distinct components of memory encoding and, consistent with previous findings, they observed unusually high levels of neural activity during these tasks in the older adults compared to the younger adults. This activity was associated with worse memory performance and atrophy of important structures in the medial temporal lobe of the older adults. Together, these findings suggest a role for Alzheimer's pathology in the memory impairment of normal aging.

The cerebral cortex — the grooved sheet of brain tissue also known as gray matter — undergoes dramatic structural changes throughout our lives, but our understanding of these changes from childhood to adulthood remains incomplete. In a new study, researchers analyzed magnetic resonance imaging (MRI) data that documented changes in brain structure in four independent groups of typically developing individuals from the United States, Norway, and the Netherlands, as they matured from age 7 to 29. The authors found that the volume, thickness, and surface area of the cortex decreased as the participants got older, and that decreases in volume were strongly related to thinning of the cortex. The results of the study also showed complex relationships between the developmental changes in cortical thickness and surface area.